The primary objective of this proposal is to determine the capacity of a large number of drugs to antagonize the reinforcing effects of cocaine. In order to achieve this objective it is first necessary to develop a procedure that will measure the reinforcing effects of cocaine in a dose-related, specific, and rapid manner. We are modifying our current procedures of intravenous cocaine self-administration in rhesus monkeys to permit the animals to self-administer a number of doses of cocaine during each daily session. The goal is to produce increases in rates of cocaine self-administration as a function of increases in dose of cocaine during each session. The procedure also includes a signaled time period during which alfentanyl, a potent opiate drug, can be self-administered. The effects of a number of drugs, including antihypertensive, antidepressant, antiparkinson's and antipsychotic agents, will be evaluated in monkeys on this paradigm. We are hopeful that some of these drugs will produce a decrease in cocaine self-administration that is related both to the dose of cocaine and the dose of the test drug. Drugs that do this without altering alfentanyl self-administration will be evaluated for reinforcing properties of their own; those that show little or no capacity to maintain self-administration behavior will be considered as potential candidates for the treatment of cocaine abuse.
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